Anti-CD146 Autoantibodies: The First Biologic Markers Associated With Occupational Exposure in Systemic Sclerosis

Our plain-English summary of Anti-CD146 Autoantibodies: The First Biologic Markers Associated With Occupational Exposure in Systemic Sclerosis, by J. Bermudez, X. Heim, E. Kaspi, et al (ACR Open Rheumatology, 2026).

The study

• Authors: J. Bermudez, X. Heim, E. Kaspi, C. Reytier, A. Beziane, R. Arcani, A. Benyamine, B. Granel, A. Villa, M. Blot-Chabaud, E. Dumontet, C. Paris, A. Lescoat, V. Lecureur, N. Bardin
• Journal: ACR Open Rheumatology
• Published: 2026;8(3):e90004
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Systemic sclerosis (SSc) is a severe autoimmune disease, with occupational exposure being a significant risk factor. Because CD146 was recently identified as a driver of fibrosis in SSc through regulation of the Wnt/reactive oxygen species interplay, we hypothesized that it is a major autoimmune target in this disease.

Methods: We developed an in-house ELISA test to detect anti-CD146 autoantibodies (AACD146), which was confirmed by immunoprecipitation and Western blotting. AACD146 positivity was assessed in the sera of patients with SSc compared with healthy controls. A validation cohort of workers exposed to asbestos or silica was evaluated and compared to patients with pulmonary cancer and healthy controls without any occupational exposure.

Results: Detection of AACD146 was assessed by ELISA and confirmed with Western blot and an absorption test. In the first cohort, the prevalence of positive AACD146 was significantly higher in patients with SSc (n = 14 of 93; 15%) than in controls (n = 2 of 40; 5%). Interestingly, among patients with SSc, positive AACD146 were associated with male sex (P = 0.04) and occupational exposure to silica (P = 0.009), with a sensitivity of 57% and specificity of 88% for occupational exposure. Results were confirmed in a validation cohort, in which positive AACD146 were found in 57% (n = 13 of 23) of patients with professional exposure. The frequency of AACD146 was significantly higher compared to controls (P = 0.03) and to patients with a history of cancer (P = 0.02).

Conclusion: We demonstrated that AACD146 are detectable in patients with SSc and are linked to male workers with occupational dust exposure. AACD146 are the first biomarkers associated with occupational exposure in SSc, with potential implications for preventive medicine.

© 2026 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

In plain English

This French brief report tested blood for antibodies against the protein CD146 with a test the authors developed. In a retrospective study of 93 Marseille patients with systemic sclerosis (scleroderma), 15% (14 of 93) tested positive, versus 5% (2 of 40) of healthy blood donors. Among these patients, a positive test was associated with male sex (P = 0.04) and occupational exposure (P = 0.009). Four of the 14 positive patients had silica exposure; of the 79 negative patients, 3 had occupational exposure, 2 to silica and 1 to aluminum. A second group from Rennes included 23 men exposed to mineral dust: silica (7), asbestos (9) or both (7). Thirteen of these 23 workers tested positive; the authors reported no significant difference between silica and asbestos exposure. None of 7 unexposed lung cancer patients and none of 3 healthy donors tested positive. The authors concluded that these antibodies are the first biomarkers associated with occupational exposure in systemic sclerosis. They noted that the retrospective design cannot show when antibodies appeared relative to exposure, and that controls were few.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Brief report: a retrospective single-centre study of patients with systemic sclerosis, plus a separate validation cohort of exposed workers and controls. Antibodies were measured with an in-house blood test (ELISA), confirmed by absorption and Western blot experiments.
• Who was studied: First cohort: 93 patients with systemic sclerosis from the Internal Medicine Department of Assistance Publique – Hôpitaux de Marseille (89% women), compared with 40 healthy blood donors. Validation cohort from Rennes University Hospital: 23 men occupationally exposed to mineral dusts (median age 55 at sampling, none with a history of cancer or autoimmune disease), compared with 7 patients with pulmonary cancer without occupational exposure and 3 healthy donors.
• Exposure: Occupational exposure to mineral dusts. In the validation cohort of 23 workers: silica in 7 (30.5%), asbestos in 9 (39%), and both in 7 (30.5%). In the systemic sclerosis cohort, 7 patients (8%) had occupational exposure, mostly to crystalline silica (n = 6); one antibody-negative patient had aluminum exposure. No asbestos exposure is reported in the systemic sclerosis cohort.
• Main results:
  • Patients with systemic sclerosis tested positive for anti-CD146 autoantibodies more often than healthy blood donors: 15% (14 of 93) versus 5% (2 of 40), P < 0.0001.
  • Among patients with systemic sclerosis, a positive test was associated with male sex (P = 0.04) and with occupational exposure (P = 0.009). For exposure in these patients, the test had a sensitivity of 57% and a specificity of 88%.
  • Among patients with systemic sclerosis, 4 of the 14 antibody-positive patients (29%) had a history of silica exposure. Among the 79 antibody-negative patients, 3 (4%) had occupational exposure: 2 to silica and 1 to aluminum.
  • In the validation cohort of workers exposed to silica, asbestos or both, 57% (13 of 23) tested positive.
  • Among the exposed workers, antibody-positive and antibody-negative workers did not differ in age, duration of exposure, or type of exposure.
  • The authors reported no significant difference between silica and asbestos exposure in the validation cohort.
  • Positive results were more frequent in exposed workers (13 of 23) than in patients with a history of pulmonary cancer but no occupational exposure (0 of 7; P = 0.02), and than in healthy donors (0 of 3; P = 0.04).
  • Among exposed workers, interstitial lung disease showed a trend toward being more common in antibody-positive workers than in antibody-negative workers (31% vs 0%). This difference was not statistically significant (P = 0.1).
  • In patients with systemic sclerosis, a positive test was not associated with specific organ involvement, such as pulmonary hypertension, or with cancer history.
• The authors' conclusion: The authors concluded that anti-CD146 autoantibodies are detectable in patients with systemic sclerosis and are linked to male workers with occupational dust exposure. They described them as the first biomarkers associated with occupational exposure in systemic sclerosis and as a proof of concept, and said that larger and longitudinal studies are needed.
• Limitations the authors state:
  • The retrospective design limits the ability to establish the timing between exposure and the appearance of the autoantibodies.
  • The study included a limited number of control patients; a larger control cohort is needed.
  • The trend toward more interstitial lung disease in antibody-positive exposed workers was not statistically significant, possibly because of the small sample size.

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Fibrosis, Reactive Oxygen Species (ROS), Biomarker.

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